Hydroxypropyl-ß-cyclodextrin spikes local inflammation that induces Th2 cell and T follicular helper cell responses to the coadministered antigen.
J Immunol
; 194(6): 2673-82, 2015 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-25681338
ABSTRACT
Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined. In this study, we reprofiled hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-ß-CD triggered the innate immune response at the injection site, was trapped by MARCO(+) macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes. It significantly enhanced Ag-specific Th2 and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum. At the injection site, HP-ß-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern. DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant. Finally, we demonstrated that HP-ß-CD-adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-ß-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-ß-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Auxiliares-Indutores
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Células Th2
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Beta-Ciclodextrinas
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Inflamação
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Antígenos
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article